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https://www.readbyqxmd.com/read/28639674/transition-from-disordered-aggregates-to-ordered-lattices-kinetic-control-of-the-assembly-of-a-computationally-designed-peptide
#1
Yu Tian, Huixi Violet Zhang, Kristi L Kiick, Jeffery G Saven, Darrin J Pochan
Natural biomolecular self-assembly typically occurs under a narrow range of solution conditions, and the design of sequences that can form prescribed structures under a range of such conditions would be valuable in the bottom-up assembly of predetermined nanostructures. We present a computationally designed peptide that robustly self-assembles into regular arrays under a wide range of solution pH and temperature conditions. Controling the solution conditions provides the opportunity to exploit a simple and reproducible approach for altering the pathway of peptide solution self-assembly...
June 22, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28636317/downsizing-proto-oncogene-cfos-to-short-helix-constrained-peptides-that-bind-jun
#2
Daniel Baxter, Samuel R Perry, Timothy A Hill, W Mei Kok, Nathan R Zaccai, R Leo Brady, David P Fairlie, Jody M Mason
The oncogenic transcription factor activator protein-1 (AP-1) is a DNA-binding protein that assembles through dimerization of Fos and Jun protein subunits, their leucine-rich helical sequences entwining into a coiled-coil structure. This study reports on downsizing the proto-oncogene cFos protein (380 residues) to shorter peptides (37-25 residues) modified with helix-inducing constraints to enhance binding to Jun. A crystal structure is reported for a 37-residue Fos-derived peptide (FosW) bound to Jun. This guided iterative downsizing of FosW to shorter peptide sequences that were constrained into stable water-soluble α-helices by connecting amino acid side chains to form cyclic pentapeptide components...
June 21, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28630153/membrane-spanning-%C3%AE-helical-barrels-as-tractable-protein-design-targets
#3
REVIEW
Ai Niitsu, Jack W Heal, Kerstin Fauland, Andrew R Thomson, Derek N Woolfson
The rational (de novo) design of membrane-spanning proteins lags behind that for water-soluble globular proteins. This is due to gaps in our knowledge of membrane-protein structure, and experimental difficulties in studying such proteins compared to water-soluble counterparts. One limiting factor is the small number of experimentally determined three-dimensional structures for transmembrane proteins. By contrast, many tens of thousands of globular protein structures provide a rich source of 'scaffolds' for protein design, and the means to garner sequence-to-structure relationships to guide the design process...
August 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28628358/h2b-ubiquitination-conserved-molecular-mechanism-diverse-physiologic-functions-of-the-e3-ligase-during-meiosis
#4
Liying Wang, Cunwei Cao, Fang Wang, Jianguo Zhao, Wei Li
RNF20/Bre1 mediated H2B ubiquitination (H2Bub) has various physiologic functions. Recently, we found that H2Bub participates in meiotic recombination by promoting chromatin relaxation during meiosis. We then analyzed the phylogenetic relationships among the E3 ligase for H2Bub, its E2 Rad6 and their partner WW domain-containing adaptor with a coiled-coil (WAC) or Lge1, and found that the molecular mechanism underlying H2Bub is evolutionarily conserved from yeast to mammals. However, RNF20 has diverse physiologic functions in different organisms, which might be caused by the evolutionary divergency of their domain/motif architectures...
June 19, 2017: Nucleus
https://www.readbyqxmd.com/read/28628237/wing-phosphorylation-is-a-major-functional-determinant-of-the-lrs14-type-biofilm-and-motility-regulator-abfr1-in-sulfolobus-acidocaldarius
#5
Lingling Li, Ankan Banerjee, Lisa Franziska Bischof, Hassan Ramadan Maklad, Lena Hoffmann, Anna-Lena Henche, Fabian Veliz, Wolfgang Bildl, Uwe Schulte, Alvaro Orell, Lars-Oliver Essen, Eveline Peeters, Sonja-Verena Albers
In response to a variety of environmental cues, prokaryotes can switch between a motile and a sessile, biofilm-forming mode of growth. The regulatory mechanisms and signaling pathways underlying this switch are largely unknown in archaea but involve small winged helix-turn-helix DNA-binding proteins of the archaea-specific Lrs14 family. Here, we study the Lrs14 member AbfR1 of Sulfolobus acidocaldarius. Small-angle X-ray scattering data are presented, which are consistent with a model of dimeric AbfR1 in which dimerization occurs via an antiparallel coiled coil as suggested by homology modeling...
June 19, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28626925/stoichiometric-analysis-of-oligomeric-states-of-three-class-a-gpcrs-chemokine-cxcr4-dopamine-d2-and-prostaglandin-ep1-receptors-on-living-cells
#6
Kenichi Kawano, Tetsuya Yagi, Nozomu Fukada, Yoshiaki Yano, Katsumi Matsuzaki
G-protein-coupled receptors (GPCRs) form the largest family of transmembrane receptors, and their oligomerization has been suggested to be related to their functions. Despite extensive studies, their oligomeric states are highly controversial. One of the reasons is the overestimation of oligomerization by conventional methods. We recently established a stoichiometric analysis method for precisely determining the oligomeric state of membrane proteins on living cells with the combined use of the coiled-coil labeling method and a spectral imaging technique and showed that the prototypical class-A GPCR β2 -adrenergic receptor (β2 AR) did not form functional oligomers...
June 18, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28624464/complex-phenotypes-associated-with-stim1-mutations-in-both-coiled-coil-and-ef-hand-domains
#7
Elizabeth Harris, Umar Burki, Chiara Marini-Bettolo, Marcella Neri, Chiara Scotton, Judith Hudson, Marta Bertoli, Teresinha Evangelista, Bas Vroling, Tuomo Polvikoski, Mark Roberts, Ana Töpf, Kate Bushby, Daniel McArthur, Hanns Lochmüller, Alessandra Ferlini, Volker Straub, Rita Barresi
Dominant mutations in STIM1 are a cause of three allelic conditions: tubular aggregate myopathy, Stormorken syndrome (a complex phenotype including myopathy, hyposplenism, hypocalcaemia and bleeding diathesis), and a platelet dysfunction disorder, York platelet syndrome. Previous reports have suggested a genotype-phenotype correlation with mutations in the N-terminal EF-hand domain associated with tubular aggregate myopathy, and a common mutation at p.R304W in a coiled coil domain associated with Stormorken syndrome...
May 4, 2017: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/28623462/in-silico-investigations-of-chemical-constituents-of-clerodendrum-colebrookianum-in-the-anti-hypertensive-drug-targets-rock-ace-and-pde5
#8
Hemant Arya, Safiulla Basha Syed, Sorokhaibam Sureshkumar Singh, Dinakar R Ampasala, Mohane Selvaraj Coumar
Understanding the molecular mode of action of natural product is a key step for developing drugs from them. In this regard, this study is aimed to understand the molecular-level interactions of chemical constituents of Clerodendrum colebrookianum Walp., with anti-hypertensive drug targets using computational approaches. The plant has ethno-medicinal importance for the treatment of hypertension and reported to show activity against anti-hypertensive drug targets-Rho-associated coiled-coil protein kinase (ROCK), angiotensin-converting enzyme, and phosphodiesterase 5 (PDE5)...
June 16, 2017: Interdisciplinary Sciences, Computational Life Sciences
https://www.readbyqxmd.com/read/28622290/structural-basis-for-the-regulatory-interactions-of-proapoptotic-par-4
#9
Udaya K Tiruttani Subhramanyam, Jan Kubicek, Ulf B Eidhoff, Joerg Labahn
Par-4 is a unique proapoptotic protein with the ability to induce apoptosis selectively in cancer cells. The X-ray crystal structure of the C-terminal domain of Par-4 (Par-4CC), which regulates its apoptotic function, was obtained by MAD phasing. Par-4 homodimerizes by forming a parallel coiled-coil structure. The N-terminal half of Par-4CC contains the homodimerization subdomain. This structure includes a nuclear export signal (Par-4NES) sequence, which is masked upon dimerization indicating a potential mechanism for nuclear localization...
June 16, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28621423/roles-of-the-cilium-associated-gene-ccdc11-in-left-right-patterning-and-in-laterality-disorders-in-humans
#10
Michal Gur, Enbal Ben-Tal Cohen, Olga Genin, Abraham Fainsod, Zeev Perles, Yuval Cinnamon
Axial determination occurs during early stages of embryogenesis. Flaws in laterality patterning result in abnormal positioning of visceral organs, as manifested in heterotaxy syndrome, or complete left-right inversion as in situs inversus totalis. These malformations are often associated with ciliopathies, as seen in primary ciliary dyskinesia. We have recently described a novel mutation in the Coiled-Coil Domain-Containing 11 (CCDC11) gene associated with laterality disorders in a consanguineous family of Arab-Muslim origin with two affected siblings presenting with diverse phenotypes, one with heterotaxy syndrome and the other with non-primary ciliary dyskinesia situs inversus totalis...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28619981/ibrutinib-unmasks-critical-role-of-bruton-tyrosine-kinase-in-primary-cns-lymphoma
#11
Christian Grommes, Alessandro Pastore, Nicolaos Palaskas, Sarah S Tang, Carl Campos, Derrek Schartz, Paolo Codega, Donna Nichol, Owen Clark, Wan-Ying Hsieh, Daniel Rohle, Marc K Rosenblum, Agnes Viale, Viviane Tabar, Cameron W Brennan, Igor T Gavrilovic, Thomas J Kaley, Craig Nolan, Antonio M P Omuro, Elena Pentsova, Alissa A Thomas, Elina Tsyvkin, Ariela Noy, M Lia Palomba, Paul A Hamlin, Craig Sauter, Craig H Moskowitz, Julia Wolfe, Ahmet Dogan, Minhee Won, Jon Glass, Scott Peak, Enrico C Lallana, Vaios Hatzoglou, Anne S Reiner, Philip Gutin, Jason T Huse, Katherine Panageas, Thomas G Graeber, Nikolaus Schultz, Lisa M DeAngelis, Ingo K Mellinghoff
Bruton tyrosine kinase (BTK) links the B-cell antigen receptor (BCR) and Toll-like receptors with Nuclear factor kappa B (NF-κB). The role of BTK in primary CNS lymphoma (PCNSL) is unknown. We performed a Phase 1 clinical trial with ibrutinib, the first-in-class BTK inhibitor, for patients with relapsed or refractory CNS Lymphoma. Clinical responses to ibrutinib occurred in 10/13 (77%) PCNSL patients, including five complete responses. The only PCNSL with complete ibrutinib resistance harbored a mutation within the coiled-coil domain of Caspase Recruitment Domain Family Member 11, a known ibrutinib resistance mechanism...
June 15, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28619510/crystal-structure-of-brlr-with-c-di-gmp
#12
Harikiran Raju, Rohan Sharma
The transcriptional regulator BrlR is a member of the MerR family of multidrug transport activators in Pseudomonas aeruginosa. Recent study indicates that BrlR is a novel 3',5'-cyclic diguanylic acid (c-di-GMP) receptor and can be activated by c-di- GMP. To gain insight into BrlR function, we determined the structure of BrlR with c-di-GMP complex structure to 2.5 Å. The structure and SEC data revealed BrlR forms a tetramer and each BrlR protomer consists of three parts, DNA-binding domain, a coiled-coil region and GyrI-like domain...
June 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28613431/a-conserved-coiled-coil-protein-pair-focuses-the-cytokinetic-z-ring-in-caulobacter-crescentus
#13
Selamawit Woldemeskel, Ryan McQuillen, Alex M Hessel, Jie Xiao, Erin D Goley
The cytoskeletal GTPase FtsZ assembles at midcell, recruits the division machinery, and directs envelope invagination for bacterial cytokinesis. ZapA, a conserved FtsZ-binding protein, promotes Z-ring stability and efficient division through a mechanism that is not fully understood. Here we investigated the function of ZapA in Caulobacter crescentus. We found that ZapA is encoded in an operon with a small coiled-coil protein we named ZauP. ZapA and ZauP co-localized at the division site and were each required for efficient division...
June 14, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28613140/influenza-virus-protein-pb1-f2-interacts-with-calcoco2-ndp52-to-modulate-innate-immune-response
#14
Olivier Leymarie, Léa Meyer, Lionel Tafforeau, Vincent Lotteau, Bruno Da Costa, Bernard Delmas, Christophe Chevalier, Ronan Le Goffic
PB1-F2 is a viral protein encoded by influenza A viruses (IAVs). PB1-F2 is implicated in virulence by triggering immune cell apoptosis and enhancing inflammation. To obtain an insight into the molecular mechanisms of PB1-F2-mediated virulence, we used the yeast two-hybrid approach to find new PB1-F2 cellular interactors. This allowed us to identify calcium-binding and coiled-coil domain 2 (CALCOCO2, also known as NDP52) as a binding partner of PB1-F2. Binding of PB1-F2 to CALCOCO2 was confirmed by pull-down...
June 14, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28606734/the-interplay-between-histone-deacetylases-and-rho-kinases-is-important-for-cancer-and-neurodegeneration
#15
REVIEW
Sonja Mertsch, Oliver H Krämer
Rho associated coiled-coil containing kinases (ROCKs) respond to defined extra- and intracellular stimuli to control cell migration, cell proliferation, and apoptosis. Histone deacetylases (HDACs) are epigenetic modifiers that regulate nuclear and cytoplasmic signaling through the deacetylation of histones and non-histone proteins. ROCK and HDAC functions are important compounds of basic and applied research interests. Recent evidence suggests a physiologically important interplay between HDACs and ROCKs in various cells and organisms...
June 1, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28605454/stacks-off-tracks-a-role-for-the-golgin-atcasp-in-plant-endoplasmic-reticulum-golgi-apparatus-tethering
#16
Anne Osterrieder, Imogen A Sparkes, Stan W Botchway, Andy Ward, Tijs Ketelaar, Norbert de Ruijter, Chris Hawes
The plant Golgi apparatus modifies and sorts incoming proteins from the endoplasmic reticulum (ER) and synthesizes cell wall matrix material. Plant cells possess numerous motile Golgi bodies, which are connected to the ER by yet to be identified tethering factors. Previous studies indicated a role for cis-Golgi plant golgins, which are long coiled-coil domain proteins anchored to Golgi membranes, in Golgi biogenesis. Here we show a tethering role for the golgin AtCASP at the ER-Golgi interface. Using live-cell imaging, Golgi body dynamics were compared in Arabidopsis thaliana leaf epidermal cells expressing fluorescently tagged AtCASP, a truncated AtCASP-ΔCC lacking the coiled-coil domains, and the Golgi marker STtmd...
June 9, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28603526/ftr83-a-member-of-the-large-fish-specific-fintrim-family-triggers-ifn-pathway-and-counters-viral-infection
#17
Christelle Langevin, Elina Aleksejeva, Armel Houel, Valérie Briolat, Corinne Torhy, Aurélie Lunazzi, Jean-Pierre Levraud, Pierre Boudinot
Tripartite motif (TRIM) proteins are involved in various cellular functions and constitute key factors of the antiviral innate immune response. TRIM proteins can bind viral particles directly, sending them to degradation by the proteasome, or ubiquitinate signaling molecules leading to upregulation of innate immunity. TRIM proteins are present in across metazoans but are particularly numerous in vertebrates where genes comprising a B30.2 domain have been often duplicated. In fish, a TRIM subset named finTRIM is highly diversified, with large gene numbers and clear signatures of positive selection in the B30...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28600863/silencing-of-lncrna-ccdc26-restrains-the-growth-and-migration-of-glioma-cells-in-vitro-and-in-vivo-via-targeting-mir-203
#18
Shilei Wang, Yuzuo Hui, Xiaoming Li, Qingbin Jia
Gliomas are the most common primary brain tumors with high mortality. The treatment for gliomas is largely limited dueto the uncomprehending pathological mechanism. Here we aimed to investigate the effect of long non-coding RNA (lncRNA) coiled-coil domain-containing 26 (CCDC26) in gliomas progression. In our study, the expression of CCDC26 was found up-regulated in gliomas tissues and cell lines compared with normal tissues and cell lines. Further exploration detected decreased cell proliferation and increased cell apoptosis in U-251 and M059J cells transfected with CCDC26-siRNA...
June 9, 2017: Oncology Research
https://www.readbyqxmd.com/read/28600229/the-structural-basis-of-alpha-tropomyosin-linked-asp230asn-familial-dilated-cardiomyopathy
#19
M L Lynn, L Tal Grinspan, T A Holeman, J Jimenez, J Strom, J C Tardiff
Recently, linkage analysis of two large unrelated multigenerational families identified a novel dilated cardiomyopathy (DCM)-linked mutation in the gene coding for alpha-tropomyosin (TPM1) resulting in the substitution of an aspartic acid for an asparagine (at residue 230). To determine how a single amino acid mutation in α-tropomyosin (Tm) can lead to a highly penetrant DCM we generated a novel transgenic mouse model carrying the D230N mutation. The resultant mouse model strongly phenocopied the early onset of cardiomyopathic remodeling observed in patients as significant systolic dysfunction was observed by 2months of age...
June 7, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28598808/mir-199a-b-5p-inhibits-hepatocellular-carcinoma-progression-by-post-transcriptionally-suppressing-rock1
#20
Yangyang Zhan, NanXin Zheng, Fei Teng, Leilei Bao, Fang Liu, Mingjian Zhang, Meng Guo, Wenyuan Guo, Guoshan Ding, Quanxing Wang
In this study, we explored the actions of miR-199a/b-5p during hepatocellular carcinoma (HCC) progression and its potential target genes. Through heatmap miRNA expression analysis of 15 matched HCC tumor and adjacent non-tumor liver tissues from the TCGA database, we detected 19 mRNAs that were upregulated and 13 that were downregulated specifically in HCC. Among these, miR-199 family members were downregulated in HCC tumors and cell lines, as compared to controls. Low miR-199a/b-5p expression was also associated with poor overall survival of HCC patients...
May 22, 2017: Oncotarget
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